Deletion of the complement phagocytic receptors CR3 and CR4 does not alter susceptibility to experimental cerebral malaria.
Deletion of the complement phagocytic receptors CR3 and CR4 does not alter susceptibility to experimental cerebral malaria.
复制标题
DOI：
10.1111/pim.12002
复制
发表时间：
2012-11
影响因子：
2.2
通讯作者：
Barnum SR
中科院分区：
文献类型：
--
作者：
Ramos TN;Bullard DC;Barnum SR
C3 衍生片段 (CR1-4) 的补体受体在先天性和适应性免疫反应中发挥着关键作用。在这些受体中，CR3 和 CR4 对于补体调理病原体（包括寄生虫）的结合和吞噬作用很重要。 CR3 和 CR4 在疟疾或脑型疟疾中的作用很少受到关注，并且在人类疾病和疟疾啮齿动物模型中仍然知之甚少。 CR3 和 CR4 是粘附分子 β2-整合素家族的成员，在参与脑型疟疾 (CM) 发展的所有白细胞上表达，最重要的是，它与寄生虫吞噬作用（单核细胞/巨噬细胞）以及抗原加工和呈递（树突细胞）有关。因此，这些受体可能在疾病发展中发挥重要作用。为了解决这个问题，我们研究了 CR3-/- 和 CR4-/- 小鼠在实验性脑疟疾 (ECM) 中的作用。我们发现 CR3-/- 和 CR4-/- 小鼠对 ECM 完全敏感，并且发展出与野生型小鼠相当的疾病。我们的结果表明，CR3 和 CR4 对于 ECM 的发病机制并不重要，尽管它们在消除补体调理病原体方面发挥着作用。这些发现支持最近的研究表明末端补体途径和膜攻击复合物在 ECM 发病机制中的重要性。
Complement receptors for C3-derived fragments (CR1-4) play critical roles in innate and adaptive immune responses. Of these receptors, CR3 and CR4 are important in binding and phagocytosis of complement-opsonized pathogens including parasites. The role of CR3 and CR4 in malaria or in cerebral malaria has received little attention and remains poorly understood in both human disease and rodent models of malaria. CR3 and CR4 are members of the β2-integrin family of adhesion molecules and are expressed on all leukocytes that participate in the development of cerebral malaria (CM), most importantly as it relates to parasite phagocytosis (monocytes/macrophages) and antigen processing and presentation (dendritic cells). Thus it is possible that these receptors might play an important role in disease development. To address this question, we examined the role of CR3-/- and CR4-/- mice in experimental cerebral malaria (ECM). We found that both CR3-/- and CR4-/- mice were fully susceptible to ECM and developed disease comparable to wild type mice. Our results indicate that CR3 and CR4 are not critical to the pathogenesis of ECM despite their role in elimination of complement-opsonized pathogens. These findings support recent studies indicating the importance of the terminal complement pathway and the membrane attack complex in ECM pathogenesis.
登录
查看更多内容
影响因子：
1.5
作者：
Awandare, Gordon A.;Spadafora, Carmenza;Moch, J. Kathleen;Dutta, Sheetij;Haynes, J. David;Stoute, Jose A.
通讯作者：
Stoute, Jose A.
影响因子：
5.4
作者：
Frick, C;Odermatt, A;Parkos, CA
通讯作者：
Parkos, CA
影响因子：
4.4
作者：
Ing, R;Segura, M;Stevenson, MM
通讯作者：
Stevenson, MM
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Perry, JA;Rush, A;Avery, AC
通讯作者：
Avery, AC